title: Liver ischemic preconditioning (IPC) improves intestinal microbiota following liver transplantation in rats through 16s rDNA-based analysis of microbial structure shift.
abstract: BACKGROUND
  Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The "gut-liver axis" closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT).
  
  
  METHODS
  The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis.
  
  
  RESULTS
  Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum.
  
  
  CONCLUSIONS
  Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the "gut-liver axis".
authors.affiliation: Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China ; Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Ren
authors.forename: Guangying
authors.initials: G
authors.lastname: Cui
authors.forename: Haifeng
authors.initials: H
authors.lastname: Lu
authors.forename: Xinhua
authors.initials: X
authors.lastname: Chen
authors.forename: Jianwen
authors.initials: J
authors.lastname: Jiang
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Songming
authors.initials: S
authors.lastname: Ding
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Hu
authors.forename: Weilin
authors.initials: W
authors.lastname: Wang
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D004275:DNA, Ribosomal / Q000235:genetics*; D005243:Feces / Q000382:microbiology; D007422:Intestines / Q000382:microbiology*; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply*; D016031:Liver Transplantation; D064307:Microbiota; D010802:Phylogeny; D051381:Rats
chemical_list: D004275:DNA, Ribosomal